Beneficial effects of calcium channel blockade on acute glomerular hemodynamic changes induced by cyclosporine

Experimental and human studies have documented that cyclosporine (CsA) acut ely reduces glomerular filtration rate (GFR). It has been reported that thi s effect can be partially prevented by calcium (Ca) channel blockade; howev er, the mechanisms by which this combination exerts its beneficial effects are unknown. We evaluated glomerular ultrafiltration determinants during ac ute CsA administration in the rat. First, we determined that maximal whole- kidney functional changes occur between 120 and 150 minutes after CsA admin istration and confirmed that pretreatment of MWF rats with the Ca channel b locker lacidipine effectively prevents a reduction in GFR. Micropuncture me asurements in CsA-treated animals showed that a reduction in GFR (0.49 +/- 0.24 v 0.88 +/- 0.26 mL/min; P < 0.05; CsA-treated v untreated rats) is ass ociated with a significant increase in glomerular capillary pressure (P-gc; 63.1 +/- 2.1 v 52.8 +/- 2.8 mm Hg; P < 0.01) and efferent arteriolar resis tance, whereas single-nephron (SN) GFR and ultrafiltration coefficient (K-f ) are both importantly reduced (34.0 +/- 11.7 v 68.9 +/- 23.8 nL/min; P < 0 .05 and 1.04 +/- 0.33 v 4.40 +/- 2.36 nL/min/mm Hg; P < 0.01,respectively). Lacidipine partially prevented SNGFR (43.1 +/- 14.3 nL/min) and K-f declin e (2.08 +/- 1.10 nL/min/mm Hg) despite the presence of elevated P-gc. This study further documents that Ca channel blockade has favorable effects on C sA-induced acute renal dysfunction. The mechanism of protection includes th e prevention of glomerular hemodynamic changes induced by CsA, mainly GFR d ecline and reduction in glomerular K-f. (C) 1999 by the National Kidney Fou ndation, Inc.